1. Field of the Invention
This invention relates to a process for the racemization of optically active phenylacetic acid derivatives of the following general formula (I). More specifically, the invention relates to a process for the racemization of optically active .alpha.-cyclopropylphenylacetic acid derivatives or .alpha.-isopropylphenylacetic acid derivatives. ##STR2## wherein X and Y, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen-substituted lower alkyl group or a halogen-substituted lower alkoxy group, or X and Y may jointly form an alkylenedioxy group; m and n, which may be the same or different, each represents an integer of 1 to 5, and the sum of m and n does not exceed 5; and R represents an isopropyl group or a cyclopropyl group.
2. Description of the Prior Art
It is already known that a group of .alpha.-substituted phenylacetic esters having a greatly different structure from conventional pyrethroid-type insecticides have a strong insecticidal activity on various noxious insects (Japanese Patent Application (OPI) Nos. 26425/74, 126826/74 and 1315563/77). (The term "OPI" as used herein refers to a "published unexamined Japanese patent application".) Among these, esters of phenylacetic acid derivatives in which the substituent in the .alpha.-position is an isopropyl or cyclopropyl group have recently attracted attention because of their superior effect. Particularly, esters of 2-(4-chlorophenyl)-3-methylbutyric acid are excellent in respect of their effect and cost economy.
Various investigations were made about the insecticidal effect of esters of optically active carboxylic acids obtained by the optical resolution of .alpha.-substituted phenylacetic acids which are the constituent element of the above-described esters. Out of these investigations, methods for the optical resolution of a series of .alpha.-substituted phenylacetic acids emerged (Japanese Patent Application (OPI) Nos. 25544/75 and 106935/75).
However, mere production of effective active isomers by optical resolution cannot generally be said to be an industrial achievement. It is not until a method of effective utilization of the separated and removed enantiomers is discovered that such a technique becomes useful. In view of this, the present inventors made extensive investigations about a method of racemizing optically active carboxylic acids and derivatives thereof with a view to effectively utilizing the separated enantiomers. In particular, as to the esters of 2-(4-chlorophenyl)-3-methylbutyric acid, those of d-isomer are more effective, and the present inventors made extensive investigations about a method of optically resolving such carboxylic acid and a method of racemizing an l-isomer thereof produced as a by-product.
Some reports have been made in the past on the racemization of optically active .alpha.-substituted phenylacetic acid derivatives.
For example, A. Horeau et al reported that optically active .alpha.-ethylphenylacetic acid chloride was easily racemized in pyridine (0.4 M solution) at room temperature and that the rate of racemization was such that the optical rotation decreased to one-seventh of its initial value in about 3 hours [Bull Soc. Chim. Fr., 117 (1967)]. In the same report, Horeau et al described that optically active .alpha.-ethylphenylacetic anhydride was racemized in pyridine at room temperature. The rate of racemization was such that the optical rotation decreased to one-half of the initial value in as long as 20 hours when the concentration of the pyridine solution was 0.1 M, while the racemization completely came to an end in about 8 hours when the concentration was 0.6 M.
H. Collet et al reported that optically active .alpha.-ethylphenylacetic acid is racemized by mixing with equimolar proportions of trifluoroacetic acid and trifluoroacetic anhydride [Tetrahedron, 28, 5883 (1972)].
Ph. Gold-Aubert reported that optically active N-.alpha.-(.alpha.-ethylphenylacetyl)urea was racemized to about 73% when heated under reflux for 90 minutes in 0.5 N NaOH in 50% aqueous ethanol [Helv. Chem. Acta., 168, 1513 (1958)].
R. S. Stuart et al examined the rate at which the hydrogen atom in the .alpha.-position of phenylacetic acids was exchanged with heavy hydrogen when the sodium salt of the phenylacetic acids was placed in deuterium oxide in the presence of an alkali. Based on this investigation, they reported that the rate of heavy hydrogen exchange was about 1/270 for sodium .alpha.-metjhylphenylacetate and about 1/42,000 for sodium .alpha.-isopropylphenylacetate based on the rate of heavy hydrogen exchange at 90.degree. C. of the sodium .alpha.-methylphenylacetate [J. Chem. Soc., Chem. Commun., 1068 (1969)].
Japanese Patent Application (OPI) No. 5134/78 discloses a process for racemizing an optically active alkali metal 2-(4-chlorophenyl)-3-methylbutyrate by heating in the presence of an alkali, etc. Japanese Patent Application (OPI) No. 3035/79 discloses that optically active 2-(4-chlorophenyl)-3-methylbutyroyl chloride can be very easily racemized by heating.
However, these processes are not directed to the racemization of carboxylic acids themselves, but pertain to the racemization of carboxylic acids in the form of various derivatives such as metal salts or acid chlorides. When the carboxylic acids are used again as a raw material for optical resolution, these derivatives should be converted back to the free acids. For this reason, at least one additional step is required, and extra reaction adjuvants are necessary.
Further investigations under the foregoing background led to the surprising discovery that optically active 2-(4-chlorophenyl)-3-methylbutyric acid can be racemized simply by heating to at least 150.degree. C., preferably to at least 200.degree. C. The present inventors also ascertained that analogous phenylacetic acid derivatives can be racemized under similar conditions. This has finally led to the accomplishment of the present invention.